The long term objective of this proposal is to develop novel antiviral drugs effective against hepatitis C virus (HCV). HCV infection in humans leads to progressive destruction of the liver resulting in cirrhosis and heightened risk of hepatocellular carcinoma. Antiviral drugs (such as interferon) have had limited success in controlling HCV-induced liver disease. Two novel molecules have been discovered both of which block HCV protein synthesis without adversely affecting the host cell. This proposal will examine direct and liposome-mediated delivery of these molecules individually and in combination to the liver of experimental animals. In addition, distribution, stability and clearance of these molecules in liver and various other organs of mice will be determined. If successful, the efficacy of these molecules in blocking HCV infection can be studied in chimpanzees. It is hoped that the experiments proposed here will lead to development of novel antiviral drugs effective against HCV infection in humans. PROPOSED COMMERCIAL APPLICATION The experiments proposed here should yield important information leading to development of novel drugs effective against HCV infection in humans.